Drinking water disinfectants react with natural organic material (NOM) present in source waters used for
drinking water to produce a wide variety of by-products. Several hundred disinfections by-products (
DBPs) have been identified, but none have been identified with sufficient carcinogenic potency to account for the
cancer risks projected from epidemiological studies. In a search for
DBPs that might fill this risk gap, the present study projected reactions of
chlorine and
chloramine that could occur with substructures present in NOM to produce novel by-products. A review of toxicological data on related compounds, supplemented by use of a quantitative structure toxicity relationship (QSTR) program TOPKAT®) identified chemicals with a high probability of being chronically toxic and/or carcinogenic among 489 established and novel
DBPs. Classes of
DBPs that were specifically examined were haloquinones (HQs), related halo-
cyclopentene and
cyclohexene (HCP&H) derivatives, halonitriles (HNs), organic N-
chloramines (NCls), haloacetamides (HAMs), and
nitrosamines (
NAs). A review of toxicological data available for
quinones suggested that HQs and HCP&H derivatives appeared likely to be of health concern and were predicted to have chronic lowest observed adverse effect levels (LOAELs) in the low μg/kg day range. Several HQs were predicted to be carcinogenic. Some have now been identified in
drinking water. The broader class of HNs was explored by considering current toxicological data on haloacetonitriles and extending this to halopropionitriles. 2,2-dichloropropionitrile has been identified in
drinking water at low concentrations, as well as the more widely recognized haloacetonitriles. The occurrence of HAMs has been previously documented. The very limited toxicological data on HAMs suggests that this class would have toxicological potencies similar to the dihaloacetic
acids. Organic N-halamines are also known to be produced in
drinking water treatment and have
biological properties of concern, but no member has ever been characterized toxicologically beyond bacterial or in vitro studies of genotoxicity. The documented formation of several
nitrosamines from secondary
amines from both natural and industrial sources prompted exploration of the formation of additional
nitrosamines. N-
diphenylnitrosamine was identified in drinking waters. Of more interest, however, was the formation of
phenazine (and subsequently N-chorophenazine) in a competing reaction. These are the first heterocyclic
amines that have been identified as chlorination by-products. Consideration of the amounts detected of members of these by-product classes and their probable toxicological potency suggest a prioritization for obtaining more detailed toxicological data of HQs>HCP&H derivatives>NCls>HNs. Based upon a ubiquitous occurrence and virtual lack of in vivo toxicological data, NCls are the most difficult group to assign a priority as potential carcinogenic risks. This analysis indicates that research on the general problem of
DBPs requires a more systematic approach than has been pursued in the past. Utilization of predictive chemical tools to guide further research can help bring resolution to the DBP issue by identifying likely
DBPs with high toxicological potency.